公开(公告)号：US20170232115A1

公开(公告)日：2017-08-17

申请号：US15380962

申请日：2016-12-15

Applicant: STC.UNM ,  Sandia Corporation

Inventor： Carlee Erin Ashley ,  C. Jeffrey Brinker ,  Eric C. Carnes ,  Mohammed Houman Fekrazad ,  Linda A. Felton ,  Oscar Negrete ,  David Patrick Padilla ,  Brian S. Wilkinson ,  Dan C. Wilkinson ,  Cheryl L. Willman

IPC: A61K49/00 ,  A61K33/24 ,  A61K31/513 ,  C12N15/113 ,  A61K38/45 ,  A61K31/506 ,  A61K38/47 ,  A61K31/465 ,  A61K31/192 ,  A61K31/704 ,  A61K48/00

CPC classification number: A61K48/0008 ,  A61K9/0014 ,  A61K9/107 ,  A61K9/1271 ,  A61K9/5078 ,  A61K31/192 ,  A61K31/465 ,  A61K31/506 ,  A61K31/513 ,  A61K31/704 ,  A61K31/7088 ,  A61K31/7105 ,  A61K31/713 ,  A61K33/24 ,  A61K38/00 ,  A61K38/17 ,  A61K38/45 ,  A61K38/47 ,  A61K45/06 ,  A61K47/6923 ,  A61K49/0082 ,  A61K49/0423 ,  B82Y5/00 ,  C07K7/06 ,  C07K2319/00 ,  C12N15/113 ,  C12N15/1131 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  C12N2810/40 ,  C12Y204/02036 ,  C12Y302/02022 ,  A61K2300/00

Abstract: The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and/or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis/cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.

公开(公告)号：US10022327B2

公开(公告)日：2018-07-17

申请号：US14970998

申请日：2015-12-16

Applicant: STC.UNM ,  SANDIA CORPORATION

Inventor： C. Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Cheryl L. Willman

IPC: A61K9/127 ,  A61K31/704 ,  A61K31/711 ,  A61K33/24 ,  A61K39/05 ,  C12N15/113 ,  C07K14/47 ,  C12N15/88 ,  A61K45/06 ,  A61K47/62 ,  A61K47/69 ,  A61K38/00 ,  A61K48/00

Abstract: The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and/or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis/cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.

公开(公告)号：US20150164798A1

公开(公告)日：2015-06-18

申请号：US14627739

申请日：2015-02-20

Applicant: STC.UNM ,  SANDIA CORPORATION

Inventor： C. Jeffrey Brinker ,  Carlee Erin Ashley ,  Xingmao Jiang ,  Juewen Liu ,  David S. Peabody ,  Walker Richard Wharton ,  Eric Carnes ,  Bryce Chackerian ,  Cheryl L. Willman

IPC: A61K9/127 ,  A61K31/704

CPC classification number: A61K9/127 ,  A61K9/1277 ,  A61K9/5115 ,  A61K9/5123 ,  A61K31/513 ,  A61K31/575 ,  A61K31/704 ,  A61K33/24 ,  A61K49/005

Abstract: Various embodiments provide materials and methods for synthesizing protocells for use in targeted delivery of cargo components to cancer cells. In one embodiment, the lipid bilayer can be fused to the porous particle core to form a protocell. The lipid bilayer can be modified with targeting ligands or other ligands to achieve targeted delivery of cargo components that are loaded within the protocell to a target cell, e.g., a type of cancer. Shielding materials can be conjugated to the surface of the lipid bilayer to reduce undesired non-specific binding.

Abstract translation: 各种实施方案提供用于合成原细胞以用于向癌细胞靶向递送货物组分的材料和方法。 在一个实施方案中，脂质双层可以与多孔颗粒核心融合以形成原细胞。 脂质双层可以用靶向配体或其他配体进行修饰，以实现载体在原细胞内的货物组分的靶向递送到靶细胞，例如一种类型的癌症。 屏蔽材料可以结合到脂质双层的表面以减少不期望的非特异性结合。

公开(公告)号：US20190091150A1

公开(公告)日：2019-03-28

申请号：US16025557

申请日：2018-07-02

Applicant: STC.UNM ,  Sandia Corporation

Inventor： C. Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Cheryl L. Willman

IPC: A61K9/127 ,  A61K31/704 ,  A61K33/24 ,  A61K47/69 ,  C07K14/47 ,  A61K45/06 ,  A61K47/62 ,  C12N15/88 ,  A61K39/05 ,  C12N15/113 ,  A61K31/711 ,  A61K48/00 ,  A61K38/00

Abstract: The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and/or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis/cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.

公开(公告)号：US09480653B2

公开(公告)日：2016-11-01

申请号：US14627739

申请日：2015-02-20

Applicant: STC.UNM ,  SANDIA CORPORATION

Inventor： C. Jeffrey Brinker ,  Carlee Erin Ashley ,  Xingmao Jiang ,  Juewen Liu ,  David S. Peabody ,  Walker Richard Wharton ,  Eric Carnes ,  Bryce Chackerian ,  Cheryl L. Willman

IPC: A61K9/56 ,  A61K9/127 ,  A61K9/51 ,  A61K49/00 ,  A61K31/575 ,  A61K31/513 ,  A61K33/24 ,  A61K31/704

CPC classification number: A61K9/127 ,  A61K9/1277 ,  A61K9/5115 ,  A61K9/5123 ,  A61K31/513 ,  A61K31/575 ,  A61K31/704 ,  A61K33/24 ,  A61K49/005

Abstract: Various embodiments provide materials and methods for synthesizing protocells for use in targeted delivery of cargo components to cancer cells. In one embodiment, the lipid bilayer can be fused to the porous particle core to form a protocell. The lipid bilayer can be modified with targeting ligands or other ligands to achieve targeted delivery of cargo components that are loaded within the protocell to a target cell, e.g., a type of cancer. Shielding materials can be conjugated to the surface of the lipid bilayer to reduce undesired non-specific binding.

公开(公告)号：US20150320681A1

公开(公告)日：2015-11-12

申请号：US14797487

申请日：2015-07-13

Applicant: STC.UNM ,  SANDIA CORPORATION

Inventor： C. Jeffrey Brinker ,  Carlee Erin Ashley ,  Xingmao Jiang ,  Juewen Liu ,  David S. Peabody ,  Walker Richard Wharton ,  Eric Carnes ,  Bryce Chackerian ,  Cheryl L. Willman

IPC: A61K9/127 ,  A61K33/24 ,  A61K31/704 ,  A61K31/513 ,  A61K49/00 ,  A61K31/575

CPC classification number: A61K9/127 ,  A61K9/1277 ,  A61K9/5115 ,  A61K9/5123 ,  A61K31/513 ,  A61K31/575 ,  A61K31/704 ,  A61K33/24 ,  A61K49/005

Abstract: Various embodiments provide materials and methods for synthesizing protocells for use in targeted delivery of cargo components to cancer cells. In one embodiment, the lipid bilayer can be fused to the porous particle core to form a protocell. The lipid bilayer can be modified with targeting ligands or other ligands to achieve targeted delivery of cargo components that are loaded within the protocell to a target cell, e.g., a type of cancer. Shielding materials can be conjugated to the surface of the lipid bilayer to reduce undesired non-specific binding.

公开(公告)号：US20180110831A1

公开(公告)日：2018-04-26

申请号：US15557000

申请日：2016-03-09

Applicant: STC.UNM

Inventor： C. Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Jacob Ongundi Agola ,  Kimberly Butler ,  Christophe Theron

IPC: A61K38/17 ,  A61K47/64 ,  A61K47/69 ,  A61K9/51 ,  C07K14/705

CPC classification number: A61K38/1774 ,  A61K9/127 ,  A61K9/5115 ,  A61K9/5123 ,  A61K47/6425 ,  A61K47/6911 ,  B82Y5/00 ,  C07K14/70546

Abstract: The present invention is directed to protocells, which have a core and a lipid bilayer surrounding the core, with at least one CD47 molecule or an active fragment thereof in or conjugated to the lipid bilayer. The CD47 present on the lipid bilayer allows the protocell to evade phagocytosis by macrophages, and can be conjugated to the lipid bilayer via a crosslinker. The protocell can be loaded with a diagnostic or therapeutic cargo, such as a polypeptide, a nucleic acid, or a drug. The protocell can also include a targeting species for targeted delivery of the cargo to a cell. The protocell can also include an endosomolytic peptide, which promotes endosomal escape after uptake by the targeted cell. The protocells with CD47 on the lipid bilayer provide better circulation after in vivo administration compared to protocells without CD47, and are therefore particularly useful as a cargo delivery vehicle.

公开(公告)号：US20160106671A1

公开(公告)日：2016-04-21

申请号：US14970998

申请日：2015-12-16

Applicant: STC.UNM ,  SANDIA CORPORATION

Inventor： C. Jeffrey Brinker ,  Eric C. Carnes ,  Carlee Erin Ashley ,  Cheryl L. Willman

IPC: A61K9/127 ,  C12N15/113 ,  A61K39/05 ,  A61K31/711 ,  A61K31/704 ,  A61K33/24

CPC classification number: A61K9/1271 ,  A61K31/704 ,  A61K31/711 ,  A61K33/24 ,  A61K38/00 ,  A61K39/05 ,  A61K45/06 ,  A61K47/62 ,  A61K47/6901 ,  A61K48/0016 ,  C07K14/47 ,  C12N15/1135 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  C12N2810/40

Abstract: The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and/or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis/cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.

Abstract translation: 本发明涉及用于特异性靶向肝细胞和其它癌细胞的原细胞，其包含具有支持的脂质双层的纳米多孔二氧化硅核心; 至少一种促进癌细胞死亡的药物（例如传统的小分子，大分子货物（例如siRNA或蛋白质毒素如蓖麻毒素A链或白喉毒素A链）和/或组蛋白包装的质粒DNA 设置在纳米多孔硅芯内（优选超螺旋以更有效地将DNA包装到原细胞中），其任选地用核定位序列修饰以帮助定位癌细胞核内的原细胞，以及表达参与治疗的肽的能力 （凋亡/细胞死亡）或作为报告物，靶向肽靶向待治疗的组织中的癌细胞，使得原细胞与靶细胞的结合是特异性和增强的，并且促进内体逃逸的融合肽 原细胞和包封的DNA。根据本发明的原细胞可用于治疗癌症，特别是包括肝细胞（肝）癌症 选择性结合肝细胞组织或在癌症诊断中起作用的新型结合肽（c-MET肽），包括癌症治疗和药物发现。

公开(公告)号：US20150272885A1

公开(公告)日：2015-10-01

申请号：US14350674

申请日：2012-10-12

Applicant: STC.UNM ,  SANDIA CORPORATION

Inventor： Carlee Erin Ashley ,  C. Jeffrey Brinker ,  Eric C. Carnes ,  Mohammad Houman Fekrazad ,  Linda A. Felton ,  Oscar Negrete ,  David Patrick Padilla ,  Brian S. Wilkinson ,  Dan C. Wilkinson ,  Cheryl L. Willman

IPC: A61K9/127 ,  A61K45/06 ,  A61K31/704 ,  A61K31/513 ,  A61K31/713 ,  A61K38/17

CPC classification number: A61K48/0008 ,  A61K9/0014 ,  A61K9/107 ,  A61K9/1271 ,  A61K9/5078 ,  A61K31/192 ,  A61K31/465 ,  A61K31/506 ,  A61K31/513 ,  A61K31/704 ,  A61K31/7088 ,  A61K31/7105 ,  A61K31/713 ,  A61K33/24 ,  A61K38/00 ,  A61K38/17 ,  A61K38/45 ,  A61K38/47 ,  A61K45/06 ,  A61K47/6923 ,  A61K49/0082 ,  A61K49/0423 ,  B82Y5/00 ,  C07K7/06 ,  C07K2319/00 ,  C12N15/113 ,  C12N15/1131 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  C12N2810/40 ,  C12Y204/02036 ,  C12Y302/02022 ,  A61K2300/00

Abstract: The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and/or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis/cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.

Abstract translation: 本发明涉及用于特异性靶向肝细胞和其它癌细胞的原细胞，其包含具有支持的脂质双层的纳米多孔二氧化硅核心; 至少一种促进癌细胞死亡的药物（例如传统的小分子，大分子货物（例如siRNA或蛋白质毒素如蓖麻毒素A链或白喉毒素A链）和/或组蛋白包装的质粒DNA 设置在纳米多孔硅芯内（优选超螺旋以更有效地将DNA包装到原细胞中），其任选地用核定位序列修饰以帮助定位癌细胞核内的原细胞，以及表达参与治疗的肽的能力 （凋亡/细胞死亡）或作为报告物，靶向肽靶向待治疗的组织中的癌细胞，使得原细胞与靶细胞的结合是特异性和增强的，并且促进内体逃逸的融合肽 原细胞和包封的DNA。根据本发明的原细胞可用于治疗癌症，特别是包括肝细胞（肝）癌症 选择性结合肝细胞组织或在癌症诊断中起作用的新型结合肽（c-MET肽），包括癌症治疗和药物发现。